Details of Disease

General Information of Disease (ID: DIS6WEHK)

• Disease Name: Opioid dependence
• Synonyms: narcotism; opioid dependence; opioid type dependence
• Disease Class: 6C43: Opioid use disorder
• Definition: Disorders related or resulting from abuse or mis-use of opioids.
• Disease Hierarchy:
  DIS9IXRC: Drug dependence
  DIS6WEHK: Opioid dependence
• ICD Code: ICD-11: ICD-11: 6C43.2Z
• Disease Identifiers:
  MONDO ID: MONDO_0005530
  MESH ID: D009293
  UMLS CUI: C0524662
  MedGen ID: 99372
  HPO ID: HP:0033515
  SNOMED CT ID: 75544000

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 7 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Buprenorphine	DMPRI8G	Approved	Small molecular drug	[1]
Ibudilast	DM4LSPN	Approved	Small molecular drug	[2]
Levomethadyl Acetate	DM06HG5	Approved	Small molecular drug	[3]
Lofexidine	DM1WXA6	Approved	Small molecular drug	[4]
Methadyl Acetate	DMIRMVB	Approved	Small molecular drug	[5]
Nalmefene	DM4YWCZ	Approved	Small molecular drug	[6]
Naloxone	DM3FXMA	Approved	Small molecular drug	[2]

This Disease is Treated as An Indication in 9 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ALKS 6428	DMUXTSG	Phase 3	NA	[2]
AD04	DMLV9GS	Phase 2	NA	[2]
GW-42003	DMXINU6	Phase 2	NA	[2]
Noribogaine	DM7ZH8Z	Phase 2	NA	[2]
OMS-403	DMUP4SY	Phase 2	NA	[7]
OMS405	DMWC36Y	Phase 2	NA	[2]
S-297995	DM26IH8	Phase 2	Small molecular drug	[8]
AIKO-150	DMW9ZFS	Phase 1	Small molecular drug	[9]
REL-1028	DMPU43M	Phase 1	NA	[2]

This Disease is Treated as An Indication in 2 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
AIKO-151	DMUQ6XH	Investigative	NA	[10]
AIKO-152	DML5Y1Q	Investigative	NA	[10]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 17 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ADCY1	TTV1ZSQ	Strong	Biomarker	[11]
CES1	TTMF541	Strong	Therapeutic	[12]
CHM	TTOA18V	Strong	Biomarker	[13]
GRIN2A	TTKJEMQ	Strong	Altered Expression	[14]
GRIN2D	TT5POTG	Strong	Altered Expression	[14]
GRK5	TTTCXO0	Strong	Biomarker	[15]
GRM6	TTWRP2F	Strong	Altered Expression	[16]
GRM7	TT0I76D	Strong	Biomarker	[17]
GRM8	TT0IFKL	Strong	Altered Expression	[16]
HCRT	TTU5HJP	Strong	Biomarker	[18]
HTR3A	TTPC4TU	Strong	Genetic Variation	[19]
NISCH	TT789FN	Strong	Altered Expression	[20]
OPRL1	TTNT7K8	Strong	Genetic Variation	[21]
PPP3CA	TTA4LDE	Strong	Genetic Variation	[22]
RGMA	TTURJV4	Strong	Genetic Variation	[23]
VIPR2	TT4O5P0	Strong	Genetic Variation	[24]
DRD2	TTEX248	Definitive	Biomarker	[25]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CNIH3	OTNLZ2QS	Limited	Biomarker	[26]
DTNBP1	OT9UQT2S	Limited	Biomarker	[27]
DISC1	OT43AW4H	moderate	Genetic Variation	[22]
NRXN3	OTJ0I7HJ	moderate	Genetic Variation	[28]
ADGRV1	OTLVXHHP	Strong	Biomarker	[29]
ANKK1	OT0OM1O0	Strong	Genetic Variation	[30]
ATP2B2	OT1NPZ9T	Strong	Biomarker	[31]
BMPER	OTBYON4H	Strong	Biomarker	[32]
C9	OT7I5FDX	Strong	Biomarker	[32]
CARTPT	OTTE4V9S	Strong	Altered Expression	[33]
DBN1	OTZVKG8A	Strong	Biomarker	[34]
KPNA3	OTLI3TM2	Strong	Genetic Variation	[35]
MYOCD	OTSJNHTH	Strong	Genetic Variation	[16]
NAV3	OT97M1TR	Strong	Biomarker	[32]
NLN	OTFRITPU	Strong	Biomarker	[36]
OPN4	OT1LZ7TS	Strong	Biomarker	[36]
PPP1R1B	OTSIJMQ9	Strong	Biomarker	[37]
TTC9	OTL29A51	Strong	Biomarker	[32]

References

• [1] Buprenorphine FDA Label
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7212).
• [4] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [5] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020315.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035962)
• [8] Clinical pipeline report, company report or official report of Shionogi (2011).
• [9] ClinicalTrials.gov (NCT00829777) Safety Study of Intravenous 6 Naltrexol (AIKO-150) in Opioid-Dependent Subjects. U.S. National Institutes of Health.
• [10] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 319).
• [11] Identification of a selective small-molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties.Sci Signal. 2017 Feb 21;10(467):eaah5381. doi: 10.1126/scisignal.aah5381.
• [12] Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat Struct Biol. 2003 May;10(5):349-56. doi: 10.1038/nsb919.
• [13] Alpha-synuclein and heroin craving in opiate-dependent patients on injectable heroin maintenance.Addict Biol. 2012 Sep;17(5):875-86. doi: 10.1111/j.1369-1600.2010.00293.x. Epub 2011 Feb 11.
• [14] Expression of NMDA receptor subunits in human blood lymphocytes: A peripheral biomarker in online computer game addiction.J Behav Addict. 2018 Jun 1;7(2):260-268. doi: 10.1556/2006.7.2018.35. Epub 2018 May 23.
• [15] GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence.Int J Neuropsychopharmacol. 2018 Oct 1;21(10):910-917. doi: 10.1093/ijnp/pyy066.
• [16] Response to methadone maintenance treatment is associated with the MYOCD and GRM6 genes.Mol Diagn Ther. 2010 Jun 1;14(3):171-8. doi: 10.1007/BF03256370.
• [17] Role of mGlu7 receptor in morphine rewarding effects is uncovered by a novel orthosteric agonist.Neuropharmacology. 2018 Mar 15;131:424-430. doi: 10.1016/j.neuropharm.2018.01.002. Epub 2018 Jan 4.
• [18] The role of orexin-1 receptor signaling in demand for the opioid fentanyl.Neuropsychopharmacology. 2019 Sep;44(10):1690-1697. doi: 10.1038/s41386-019-0420-x. Epub 2019 May 21.
• [19] From mouse to man: the 5-HT3 receptor modulates physical dependence on opioid narcotics.Pharmacogenet Genomics. 2009 Mar;19(3):193-205. doi: 10.1097/FPC.0b013e328322e73d.
• [20] The role of IRAS/Nischarin involved in the development of morphine tolerance and physical dependence.Biochem Biophys Res Commun. 2019 May 7;512(3):460-466. doi: 10.1016/j.bbrc.2019.03.055. Epub 2019 Mar 20.
• [21] Evidence for association of two variants of the nociceptin/orphanin FQ receptor gene OPRL1 with vulnerability to develop opiate addiction in Caucasians.Psychiatr Genet. 2010 Apr;20(2):65-72. doi: 10.1097/YPG.0b013e32833511f6.
• [22] DISC1 as a Possible Genetic Contribution to Opioid Dependence in a Polish Sample.J Stud Alcohol Drugs. 2016 Mar;77(2):220-6. doi: 10.15288/jsad.2016.77.220.
• [23] Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans.Biol Psychiatry. 2018 Nov 15;84(10):762-770. doi: 10.1016/j.biopsych.2017.12.016. Epub 2018 Jan 11.
• [24] A 3' UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction.PLoS One. 2019 Nov 5;14(11):e0224399. doi: 10.1371/journal.pone.0224399. eCollection 2019.
• [25] Association between dopamine D2 receptor gene polymorphisms and the risk of heroin dependence.Genet Mol Res. 2016 Nov 3;15(4). doi: 10.4238/gmr15048772.
• [26] Structural basis for preferential binding of human TCF4 to DNA containing 5-carboxylcytosine.Nucleic Acids Res. 2019 Sep 19;47(16):8375-8387. doi: 10.1093/nar/gkz381.
• [27] Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia.Eur Psychiatry. 2015 Jun;30(4):486-91. doi: 10.1016/j.eurpsy.2015.01.008. Epub 2015 Feb 16.
• [28] Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms.Hum Mol Genet. 2007 Dec 1;16(23):2880-91. doi: 10.1093/hmg/ddm247. Epub 2007 Sep 4.
• [29] Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans.Sci Rep. 2019 Dec 2;9(1):18070. doi: 10.1038/s41598-019-53560-0.
• [30] Association between the traditional Chinese medicine pathological factors of opioid addiction and DRD2/ANKK1 TaqIA polymorphisms.BMC Complement Altern Med. 2015 Jul 3;15:209. doi: 10.1186/s12906-015-0727-z.
• [31] Genome-wide association meta-analysis of age at first cannabis use.Addiction. 2018 Nov;113(11):2073-2086. doi: 10.1111/add.14368. Epub 2018 Aug 19.
• [32] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
• [33] Evaluation of CART peptide level in rat plasma and CSF: Possible role as a biomarker in opioid addiction.Peptides. 2016 Oct;84:1-6. doi: 10.1016/j.peptides.2016.06.010. Epub 2016 Jun 24.
• [34] A novel role for the actin-binding protein drebrin in regulating opiate addiction.Nat Commun. 2019 Sep 12;10(1):4140. doi: 10.1038/s41467-019-12122-8.
• [35] KPNA3 variation is associated with schizophrenia, major depression, opiate dependence and alcohol dependence. Dis Markers. 2012;33(4):163-70. doi: 10.3233/DMA-2012-0921.
• [36] Morphine-dependent and abstinent mice are characterized by a broader distribution of the neurons co-expressing mu and delta opioid receptors.Neuropharmacology. 2019 Jul 1;152:30-41. doi: 10.1016/j.neuropharm.2019.03.009. Epub 2019 Mar 8.
• [37] Nanotherapeutic approach for opiate addiction using DARPP-32 gene silencing in an animal model of opiate addiction.J Neuroimmune Pharmacol. 2015 Mar;10(1):136-52. doi: 10.1007/s11481-015-9585-1. Epub 2015 Jan 22.